erial D act is b ea o s c e y s M Mycobacterial Diseases Changal and Raina, J Mycobac Dis 2014, 4:2 DOI: 10.4172/2161-1068.1000146 ISSN: 2161-1068 Review Article Open Access Central Nervous System Manifestations of Tuberculosis: A Review Article Khalid Hamid Changal* and Ab Hameed Raina Internal Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India *Corresponding author: Khalid Hamid Changal, Internal Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India, Tel: 911942401013; E-mail: [email protected] Received date: Feb 12, 2014; Accepted date: Mar 25, 2014; Published date: Mar 29, 2014 Copyright: © 2014 Changal KH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Tuberculosis can involve almost any organ of the body. In the central nervous system (CNS) it can cause meningitis, tuberculoma, abscess, or other manifestations. Around 10% of all patients with tuberculosis have CNS involvement. Tuberculosis is rampant in the developing world and has reemerged as a major public health menace with the HIV pandemic. Compared with HIV-negative individuals, HIV-positive individuals with TB are 5 times more likely to have CNS involvement. We review the CNS manifestations of tuberculosis here in this article. Keywords: Tuberculoma; Meningitis; Alcoholism; Vessels [17-19].The most serious consequence of TBM, however, is the development of vasculitis in the vessels of the circle of Willis, the Introduction vertebrobasilar system, and the perforating branches of the middle cerebral artery, resulting in infarctions in the distribution of these In about 1% of individuals with Mycobacterium vessels. Direct contact of the exudate with the brain surface causes a tuberculosis infection, central nervous system (CNS) involvement border zone reaction that damages the underlying brain tissue. Rich develops, including meningitis, tuberculoma, abscess, or other and Mc Cordock ascribed most of these changes to a hypersensitivity manifestations [1]. The incidence of tuberculosis varies from 9 cases response [20,21]. per 100 000 population per year in the US to 110–165 cases per 100 000 population in the developing countries of Asia and Africa [2-4]. Clinical features Tuberculous involvement of the central nervous system (CNS) is an important and serious type of extra-pulmonary involvement. It has TB meningitis accounts for 5% of all extra pulmonary TB and is one been estimated that approximately 10% of all patients with of the most devastating manifestations of TB infection [22]. It occurs tuberculosis have CNS involvement [5]. In the largest prospective more frequently in children, particularly those <1 year of age [23,24]. epidemiological study on CNS tuberculosis, the chance of developing Of adults with TB meningitis, 40%–66% have extrameningeal TB at CNS tuberculosis was 1.0% among 82,764 tuberculosis cases from the time of diagnosis [25]. The most common symptoms of TB 1970 to 2001 in a Canadian cohort [1]. Several risk factors for CNS meningitis include fever, headache, vomiting, and altered level of tuberculosis have been identified. Both children [6] and HIV co consciousness. Children are more likely to present with seizures, infected patients [7-9] are at high risk for developing CNS nausea, and vomiting; headache is less frequent [26]. The basilar tuberculosis. Other risk factors include malnutrition and recent meninges and cistern are frequently affected and cause cranial nerve measles in children [10] and alcoholism, malignancies, and the use of dysfunction, especially of the sixth (abducens) and seventh (facial) immunosuppressive agents in adults [11-13]. Studies conducted in cranial nerves [27,28]. Hydrocephalus is common during TB developed countries have also identified that foreign-born individuals meningitis owing to high protein levels causing obstruction of (individuals born outside of developed countries are overrepresented cerebrospinal fluid (CSF) flow [29]. Intracranial vasculopathy is also among CNS tuberculosis cases [14,1]. Extra pulmonary manifestations frequent in TB meningitis, and stroke can occur as a complication of appear in ∼40% of HIV-infected patients with TB [15]. Compared vasospasm, thrombosis, vasculitis, or hemorrhagic infarction [30]. In with HIV-negative individuals, HIV-positive individuals with TB are 5 HIV-infected patients, TB is more likely to produce meningitis [31]. times more likely to have CNS involvement [16]. Diagnosis Tuberculous meningitis In tuberculous meningitis there is a thick, gelatinous exudate Clinical around the sylvian fissures, basal cisterns, brainstem, and cerebellum. 1. Fever and headache (for more than 14 days) Hydrocephalus may occur as a consequence of obstruction of the basal cisterns, outflow of the fourth ventricle, or occlusion of the cerebral 2. Vomiting aqueduct. Hydrocephalus frequently develops in children and is 3. Altered sensorium or focal neurological deficit associated with a poor prognosis. The basal exudates of tuberculosis are usually more severe in the vicinity of the circle of Willis, and CSF produce a vasculitis-like syndrome. Cerebral infarctions are most common around the sylvian fissure and in the basal ganglion. 1. Pleocytosis (more than 20 cells, more than 60% lymphocytes) Hemorrhagic transformation of infarcted tissue is not unusual J Mycobac Dis Volume 4 • Issue 2 • 1000146 ISSN:2161-1068 MDTL, an open access journal Citation: Changal KH, Raina AH (2014) Central Nervous System Manifestations of Tuberculosis: A Review Article. J Mycobac Dis 4: 146. doi: 10.4172/2161-1068.1000146 Page 2 of 5 2. Increased proteins (more than 100 mg/dl) considered pathognomonic of tuberculoma[38].The MRI features of tuberculoma depend on whether the lesion is non-caseating, caseating 3. Low sugar (less than 60% of corresponding blood sugar) with a solid centre, or caseating with a liquid centre. The non- 4. India ink studies and microscopy for malignant cells shouldbe caseating granulomas are hypointense on T1-weighted images and negative hyperintense on T2-weighted images; after contrast administration the lesion usually shows homogenous enhancement. The second type of Imaging tuberculoma ishypointense or isointense on T1-weighted images and also on T2-weighted image. After contrast administration there is ring 1. Exudates in basal cisterns or in sylvian fissure hydrocephalus enhancement. These types of granuloma have variable degree of 2. Infarcts (basal ganglionic) perilesionaloedema. The MRI features of tuberculoma depend on whether the lesion is non-caseating, caseating with a solid centre, or 3. Gyral enhancement caseating with a liquid centre. The non-caseating granulomas are 4. Tuberculoma formation hypointense on T1-weighted images and hyperintense on T2-weighted images; after contrast administration the lesion usually shows 5. Evidence of tuberculosis elsewhere homogenous enhancement. The second type of tubercular ishypointense or isointense on T1-weighted images and also on T2- Treatment weighted image. After contrast administration there is ring enhancement. These types of granuloma have variable degree of Given the low sensitivity of existing CSF tests for detecting TB and perilesionaloedema. Stereotactic diagnostic biopsy can help in the slow growth of M. tuberculosis in culture, anti-tuberculous establishing an accurate diagnosis [39]. treatment is often initiated empirically. Treatment is more complex for tuberculoma (tuberculous granuloma),multidrug-resistant TB (MDR TB; resistant to isoniazid [INH] and rifampicin) and extensively drug- Intracranial tuberculous abscess resistant TB (resistant to INH, rifampin, fluoroquinolones, Tuberculous brain abscess is a condition distinct from CNS capreomycin, kanamycin, and amikacin).The use of corticosteroids is tuberculoma. In developing countries tuberculous abscesses have been widely accepted as adjuvant therapy for CNS TB, particularly for TB reported in 4% to 7.5% of patients with CNS tuberculosis. The meningitis, as well as for CNS TB-associated IRIS [32] or patients with histopathological diagnosis of tuberculous brain abscess depends on pulmonary TB and HIV infection who have not recently initiated the following criteria: microscopic evidence of pus in the abscess antiretroviral therapy (ART), emerging evidence supports early cavity, microscopic changes in the abscess wall, and isolation of M initiation of ART to reduce mortality—especially in patients with CD4 tuberculosis [40]. Abscesses are usually solitary and larger and cell counts <50 cells/mm3-despite the increased incidence of IRIS [33]. progress much more rapidly than tuberculomas. CT and MRI pictures The WHO recommends initiation of ART after starting TB treatment of a tuberculous abscess show a granuloma with a liquid centre, irrespective of CD4 cell count; however, timing of ART initiation in however, they are much larger and frequently multiloculated and with patients with TB meningitis has not been addressed and may differ. marked surrounding oedema. Clinical features include partial seizures, Tuberculomas are firm, avascular, spherical granulomatous masses, focal neurological deficit, and raised intracranial tension [41]. Surgical measuring about 2–8 cm in diameter. They are well limited from exploration and drainage of pus may produce excellent long-term surrounding brain tissue which is compressed around